Use of alloplastic implants for correction of deviated nasal septum: Systematic review and meta-analysis.

PURPOSE: To systematically reviews the safety and effectiveness of alloplastic implants (AI) in septoplasty. METHODS: We conducted a comprehensive search in Medline, EMBASE, SCOPUS, CINAHL, and Cochrane Library databases to identify articles on septoplasty using AI. We also manually searched reference lists of included articles. Inclusion criteria involved prospective or retrospective case-series studies of adults with deviated nasal septum (DNS) who underwent septoplasty with AI, with sufficient follow-up data. Two authors independently screened articles, reviewed full manuscripts, and extracted data. RESULTS: Out of 5370 articles, 16 met inclusion criteria, encompassing 884 patients from 14 eligible studies. Most studies had fair quality. AI materials included Polydioxanone (PDS), Polycaprolactone (PCL), Titanium, Macropore, and PolyMax. AI usage improved nasal obstruction in most patients, with 95.6 % (84.8 %-100 %) based on physical examination and 96.9 % (89.6 %-100 %) based on symptoms. AI-related complications occurred in 4.3 % (0 %-12.8 %) of cases, mostly non-serious. CONCLUSIONS: AI use can be considered as a useful adjunct in septoplasty, with uncommon complications similar to standard procedures. However, due to limited-quality evidence, further prospective controlled studies are needed.

Information and Communication Technologies (ICTs) enabling integrated primary care for complex patients: a protocol for a scoping review.

INTRODUCTION: An increasing number of individuals are living with multiple chronic conditions, often combined with psychosocial complexities. For these patients with complex conditions, an integrated primary care model that provides care coordination and a team-based approach can help manage their multiple needs. Information and communication technologies (ICTs) are recognized as a critical enabler of integrated primary care. A better understanding of the use of ICTs in an integrated care setting and how ICTs are being leveraged would be beneficial to identify knowledge gaps and could lead to successful implementation for ICT-based interventions. OBJECTIVE: This study will systematically scope the literature on the topic of ICT-enabled integrated healthcare delivery models for patients with complex care needs to identify which technologies have been used in integrated primary care settings. METHOD: This study protocol outlines a scoping review of the peer-reviewed literature, using Arksey and O'Malley's (enhanced by Levac et al.) scoping review methodology. Peer-reviewed literature will be identified using a multi-database search strategy. The results of the search will be screened, abstracted, and charted in duplicate by six research team members. DISCUSSION: The key findings of the study will be thematically analyzed to describe the implemented ICTs aimed for complex patients within the integrated primary care model. The finding will highlight what types of ICTs are being put in place to support these models, and how these ICTs are enabling care integration. This review will be the first step to formally identify how ICT is used to support integrated primary health care models. The results will be disseminated through peer-reviewed publications, conference presentations, and special interest groups.

Recommendations for the Design and Delivery of Transitions-Focused Digital Health Interventions: Rapid Review.

BACKGROUND: Older adults experience a high risk of adverse events during hospital-to-home transitions. Implementation barriers have prevented widespread clinical uptake of the various digital health technologies that aim to support hospital-to-home transitions. OBJECTIVE: To guide the development of a digital health intervention to support transitions from hospital to home (the Digital Bridge intervention), the specific objectives of this review were to describe the various roles and functions of health care providers supporting hospital-to-home transitions for older adults, allowing future technologies to be more targeted to support their work; describe the types of digital health interventions used to facilitate the transition from hospital to home for older adults and elucidate how these interventions support the roles and functions of providers; describe the lessons learned from the design and implementation of these interventions; and identify opportunities to improve the fit between technology and provider functions within the Digital Bridge intervention and other transition-focused digital health interventions. METHODS: This 2-phase rapid review involved a selective review of providers' roles and their functions during hospital-to-home transitions (phase 1) and a structured literature review on digital health interventions used to support older adults' hospital-to-home transitions (phase 2). During the analysis, the technology functions identified in phase 2 were linked to the provider roles and functions identified in phase 1. RESULTS: In phase 1, various provider roles were identified that facilitated hospital-to-home transitions, including navigation-specific roles and the roles of nurses and physicians. The key transition functions performed by providers were related to the 3 categories of continuity of care (ie, informational, management, and relational continuity). Phase 2, included articles (n=142) that reported digital health interventions targeting various medical conditions or groups. Most digital health interventions supported management continuity (eg, follow-up, assessment, and monitoring of patients' status after hospital discharge), whereas informational and relational continuity were the least supported. The lessons learned from the interventions were categorized into technology- and research-related challenges and opportunities and informed several recommendations to guide the design of transition-focused digital health interventions. CONCLUSIONS: This review highlights the need for Digital Bridge and other digital health interventions to align the design and delivery of digital health interventions with provider functions, design and test interventions with older adults, and examine multilevel outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-045596.

Human factors applications in the design of decision support systems for population health: a scoping review.

INTRODUCTION: Public health professionals engage in complex cognitive tasks, often using evidence-based decision support tools to bolster their decision-making. Human factors methods take a user-centred approach to improve the design of systems, processes, and interfaces to better support planning and decision-making. While human factors methods have been applied to the design of clinical health tools, these methods are limited in the design of tools for population health. The objective of this scoping review is to develop a comprehensive understanding of how human factors techniques have been applied in the design of population health decision support tools. METHODS AND ANALYSIS: The scoping review will follow the methodology and framework proposed by Arksey and O'Malley. We include English-language documents between January 1990 and August 2021 describing the development, validation or application of human factors principles to decision support tools in population health. The search will include Ovid MEDLINE: Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE 1946-present; EMBASE, Scopus, PsycINFO, Compendex, IEEE Xplore and Inspec. The results will be integrated into Covidence. First, the abstract of all identified articles will be screened independently by two reviewers with disagreements being resolved by a third reviewer. Next, the full text for articles identified as include or inconclusive will be reviewed by two independent reviewers, leading to a final decision regarding inclusion. Reference lists of included articles will be manually screened to identify additional studies. Data will be extracted by one reviewer, verified by a second, and presented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. ETHICS AND DISSEMINATION: Ethics approval is not required for this work as human participants are not involved. The completed review will be published in a peer-reviewed, interdisciplinary journal.

Synthesising evidence regarding hospital to home transitions supported by volunteers of third sector organisations: a scoping review protocol.

INTRODUCTION: Given the risks inherent in care transitions, it is imperative that patients discharged from hospital to home receive the integrated care services necessary to ensure a successful transition. Despite efforts by the healthcare sector to develop health system solutions to improve transitions, problems persist. Research on transitional support has predominantly focused on services delivered by healthcare professionals; the evidence for services provided by lay navigators or volunteers in this context has not been synthesised. This scoping review will map the available literature on the engagement of volunteers within third sector organisations supporting adults in the transition from hospital to home. METHODS AND ANALYSIS: Using the well-established scoping review methodology outlined by the Joanna Briggs Institute, a five-stage review is outlined: (1) determining the research question, (2) search strategy, (3) inclusion criteria, (4) data extraction and (5) analysis and presentation of the results. The search strategy will be applied to 10 databases reflecting empirical and grey literature. A two-stage screening process will be used to determine eligibility of articles. To be included in the review, articles must describe a community-based programme delivered by a third sector organisation that engages volunteers in the provisions of services that support adults transitioning from hospital to home. All articles will be independently assessed for eligibility, and data from eligible articles will be extracted and charted using a standardised form. Extracted data will be analysed using narrative and descriptive analyses. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review. Members of an international special interest group focused on the voluntary sector will be consulted to provide insight and feedback on study findings, help with dissemination of the results and engage in the development of future research proposals. Dissemination activities will include peer-reviewed publications and academic presentations.

How digital health solutions align with the roles and functions that support hospital to home transitions for older adults: a rapid review study protocol.

INTRODUCTION: Older adults may experience challenges during the hospital to home transitions that could be mitigated by digital health solutions. However, to promote adoption in practice and realise benefits, there is a need to specify how digital health solutions contribute to hospital to home transitions, particularly pertinent in this era of social distancing. This rapid review will: (1) elucidate the various roles and functions that have been developed to support hospital to home transitions of care, (2) identify existing digital health solutions that support hospital to home transitions of care, (3) identify gaps and new opportunities where digital health solutions can support these roles and functions and (4) create recommendations that will inform the design and structure of future digital health interventions that support hospital to home transitions for older adults (eg, the pre-trial results of the Digital Bridge intervention; ClinicalTrials.gov Identifier: NCT04287192). METHODS AND ANALYSIS: A two-phase rapid review will be conducted to meet identified aims. In phase 1, a selective literature review will be used to generate a conceptual map of the roles and functions of individuals that support hospital to home transitions for older adults. In phase 2, a search on MEDLINE, EMBASE and CINAHL will identify literature on digital health solutions that support hospital to home transitions. The ways in which digital health solutions can support the roles and functions that facilitate these transitions will then be mapped in the analysis and generation of findings. ETHICS AND DISSEMINATION: This protocol is a review of the literature and does not involve human subjects, and therefore, does not require ethics approval. This review will permit the identification of gaps and new opportunities for digital processes and platforms that enable care transitions and can help inform the design and implementation of future digital health interventions. Review findings will be disseminated through publications and presentations to key stakeholders.

Relationships between ovarian hormone concentrations and mental rotations performance in naturally-cycling women.

Circulating gonadal hormones have been linked to variation in the structure and function of the adult human brain, raising the question of how cognition is affected by sex hormones in adulthood. The impacts of progestogens and estrogens are of special interest due to the widespread use of hormone supplementation. Multiple studies have analyzed relationships between ovarian hormones and mental rotation performance, one of the largest known cognitive sex differences; however, results are conflicting. These discrepancies are likely due in part to modest sample sizes and reliance on self-report measures to assess menstrual cycle phase. The present study aimed to clarify the impact of progestogens and estrogens on visuospatial cognition by relating mental rotation task performance to salivary hormone concentrations. Across two studies totaling 528 naturally-cycling premenopausal women, an internal meta-analysis suggested a small, positive effect of within-subjects changes in progesterone on MRT performance (estimate = 0.44, p = 0.014), though this result should be interpreted with caution given multiple statistical analyses. Between-subjects differences and within-subject changes in estradiol did not significantly predict MRT. These results shed light on the potential cognitive effects of endogenous and exogenous hormone action, and the proximate mechanisms modulating spatial cognition.

Multidisciplinary care for opioid dose reduction in patients with chronic non-cancer pain: A systematic realist review.

CONTEXT: Opioid related deaths are at epidemic levels in many developed nations globally. Concerns about the contribution of prescribed opioids, and particularly high-dose opioids, continue to mount as do initiatives to reduce prescribing. Evidence around opioid tapering, which can be challenging and potentially hazardous, is not well developed. A recent national guideline has recognized this and recommended referral to multidisciplinary care for challenging cases of opioid tapering. However, multidisciplinary care for opioid tapering is not well understood or defined. OBJECTIVE: Identify the existing literature on any multidisciplinary care programs that evaluate impact on opioid use, synthesize how these programs work and clarify whom they benefit. STUDY DESIGN: Systematic rapid realist review. DATASET: Bibliographic databases (MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library), grey literature, reference hand search and formal expert consultation. RESULTS: 95 studies were identified. 75% of the programs were from the United States and the majority (n = 62) were published after 2000. A minority (n = 23) of programs reported on >12 month opioid use outcomes. There were three necessary but insufficient mechanisms common to all programs: pain relief, behavior change and active medication management. Programs that did not include a combination of all three mechanisms did not result in opioid dose reductions. A concerning 20-40% of subjects resumed opioid use within one year of program completion. CONCLUSIONS: Providing alternative analgesia is insufficient for reducing opioid doses. Even high quality primary care multidisciplinary care programs do not reduce prescribed opioid use unless there is active medication management accomplished by changing the primary opioid prescriber. Rates of return to use of opioids from these programs are very concerning in the current context of a highly potent and lethal street drug supply. This contextual factor may be powerful enough to undermine the modest benefits of opioid dose reduction via multidisciplinary care.

Stress testing journals: a quasi-experimental study of rejection rates of a previously published paper.

BACKGROUND: When a journal receives a duplicate publication, the ability to identify the submitted work as previously published, and reject it, is an assay to publication ethics best practices. The aim of this study was to evaluate how three different types of journals, namely open access (OA) journals, subscription-based journals, and presumed predatory journals, responded to receiving a previously published manuscript for review. METHODS: We performed a quasi-experimental study in which we submitted a previously published article to a random sample of 602 biomedical journals, roughly 200 journals from each journal type sampled: OA journals, subscription-based journals, and presumed predatory journals. Three hundred and three journals received a Word version in manuscript format, while 299 journals received the formatted publisher's PDF version of the published article. We then recorded responses to the submission received after approximately 1 month. Responses were reviewed, extracted, and coded in duplicate. Our primary outcome was the rate of rejection of the two types of submitted articles (PDF vs Word) within our three journal types. RESULTS: We received correspondence back from 308 (51.1%) journals within our study timeline (32 days); (N = 46 predatory journals, N = 127 OA journals, N = 135 subscription-based journals). Of the journals that responded, 153 received the Word version of the paper, while 155 received the PDF version. Four journals (1.3%) accepted our paper, 291 (94.5%) journals rejected the paper, and 13 (4.2%) requested a revision. A chi-square test looking at journal type, and submission type, was significant (χ2 (4) = 23.50, p < 0.001). All four responses to accept our article came from presumed predatory journals, 3 of which received the Word format and 1 that received the PDF format. Less than half of journals that rejected our submissions did so because they identified ethical issues such as plagiarism with the manuscript (133 (45.7%)). CONCLUSION: Few journals accepted our submitted paper. However, our findings suggest that all three types of journals may not have adequate safeguards in place to recognize and act on plagiarism or duplicate submissions.

Do evidence summaries increase health policy-makers' use of evidence from systematic reviews? A systematic review.

This review summarizes the evidence from six randomized controlled trials that judged the effectiveness of systematic review summaries on policymakers' decision making, or the most effective ways to present evidence summaries to increase policymakers' use of the evidence. This review included six randomized controlled studies. A randomized controlled study is one in which the participants are divided randomly (by chance) into separate groups to compare different treatments or other interventions. This method of dividing people into groups means that the groups will be similar and that the effects of the treatments they receive will be compared more fairly. At the time the study is done, it is not known which treatment is the better one. The researchers who did these studies invited people from Europe, North America, South America, Africa, and Asia to take part in them. Two studies looked at "policy briefs," one study looked at an "evidence summary," two looked at a "summary of findings table," and one compared a "summary of findings table" to an evidence summary. None of these studies looked at how policymakers directly used evidence from systematic reviews in their decision making, but two studies found that there was little to no difference in how they used the summaries. The studies relied on reports from decision makers. These studies included questions such as, "Is this summary easy to understand?" Some of the studies looked at users' knowledge, understanding, beliefs, or how credible (trustworthy) they believed the summaries to be. There was little to no difference in the studies that looked at these outcomes. Study participants rated the graded entry format higher for usability than the full systematic review. The graded entry format allows the reader to select how much information they want to read. The study participants felt that all evidence summary formats were easier to understand than full systematic reviews. Plain language summary: Policy briefs make systematic reviews easier to understand but little evidence of impact on use of study findings: It is likely that evidence summaries are easier to understand than complete systematic reviews. Whether these summaries increase the use of evidence from systematic reviews in policymaking is not clear.What is this review about?: Systematic reviews are long and technical documents that may be hard for policymakers to use when making decisions. Evidence summaries are short documents that describe research findings in systematic reviews. These summaries may simplify the use of systematic reviews.Other names for evidence reviews are policy briefs, evidence briefs, summaries of findings, or plain language summaries. The goal of this review was to learn whether evidence summaries help policymakers use evidence from systematic reviews. This review also aimed to identify the best ways to present the evidence summary to increase the use of evidence.What are the main findings of this review?: This review included six randomized controlled studies. A randomized controlled study is one in which the participants are divided randomly (by chance) into separate groups to compare different treatments or other interventions. This method of dividing people into groups means that the groups will be similar and that the effects of the treatments they receive will be compared more fairly. At the time the study is done, it is not known which treatment is the better one.The researchers who did these studies invited people from Europe, North America, South America, Africa, and Asia to take part in them. Two studies looked at "policy briefs," one study looked at an "evidence summary," two looked at a "summary of findings table," and one compared a "summary of findings table" to an evidence summary.None of these studies looked at how policymakers directly used evidence from systematic reviews in their decision making, but two studies found that there was little to no difference in how they used the summaries. The studies relied on reports from decision makers. These studies included questions such as, "Is this summary easy to understand?"Some of the studies looked at users' knowledge, understanding, beliefs, or how credible (trustworthy) they believed the summaries to be. There was little to no difference in the studies that looked at these outcomes. Study participants rated the graded entry format higher for usability than the full systematic review. The graded entry format allows the reader to select how much information they want to read.. The study participants felt that all evidence summary formats were easier to understand than full systematic reviews.What do the findings of this review mean?: Our review suggests that evidence summaries help policymakers to better understand the findings presented in systematic reviews. In short, evidence summaries should be developed to make it easier for policymakers to understand the evidence presented in systematic reviews. However, right now there is very little evidence on the best way to present systematic review evidence to policymakers.How up to date is this review?: The authors of this review searched for studies through June 2016. Executive summary/Abstract: Background: Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which makes them hard to use for decision-making. Strategies to promote the use of evidence to decision makers are required, and evidence summaries have been suggested as a facilitator. Evidence summaries include policy briefs, briefing papers, briefing notes, evidence briefs, abstracts, summary of findings tables, and plain language summaries. There are many organizations developing and disseminating systematic review evidence summaries for different populations or subsets of decision makers. However, evidence on the usefulness and effectiveness of systematic review summaries is lacking. We present an overview of the available evidence on systematic review evidence summaries.Objectives: This systematic review aimed to 1) assess the effectiveness of evidence summaries on policy-makers' use of the evidence and 2) identify the most effective summary components for increasing policy-makers' use of the evidence.Search methods: We searched several online databases (Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Global Health Library, Popline, Africa-wide, Public Affairs Information Services, Worldwide Political Science Abstracts, Web of Science, and DfiD), websites of research groups and organizations which produce evidence summaries, and reference lists of included summaries and related systematic reviews. These databases were searched in March-April, 2016.Selection criteria: Eligible studies included randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-after (CBA) studies, and interrupted time series (ITS) studies. We included studies of policymakers at all levels as well as health system managers. We included studies examining any type of "evidence summary", "policy brief", or other product derived from systematic reviews that presented evidence in a summarized form. These interventions could be compared to active comparators (e.g. other summary formats) or no intervention.The primary outcomes were: 1) use of systematic review summaries decision-making (e.g. self-reported use of the evidence in policy-making, decision-making) and 2) policymaker understanding, knowledge, and/or beliefs (e.g. changes in knowledge scores about the topic included in the summary). We also assessed perceived relevance, credibility, usefulness, understandability, and desirability (e.g. format) of the summaries.Results: Our database search combined with our grey literature search yielded 10,113 references after removal of duplicates. From these, 54 were reviewed in full text and we included 6 studies (reported in 7 papers, 1661 participants) as well as protocols from 2 ongoing studies. Two studies assessed the use of evidence summaries in decision-making and found little to no difference in effect. There was also little to no difference in effect for knowledge, understanding or beliefs (4 studies) and perceived usefulness or usability (3 studies). Summary of Findings tables and graded entry summaries were perceived as slightly easier to understand compared to complete systematic reviews. Two studies assessed formatting changes and found that for Summary of Findings tables, certain elements, such as reporting study event rates and absolute differences were preferred as well as avoiding the use of footnotes. No studies assessed adverse effects. The risks of bias in these studies were mainly assessed as unclear or low however, two studies were assessed as high risk of bias for incomplete outcome data due to very high rates of attrition.Authors' conclusions: Evidence summaries may be easier to understand than complete systematic reviews. However, their ability to increase the use of systematic review evidence in policymaking is unclear.

Do evidence summaries increase health policy-makers use of evidence from systematic reviews?

Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which makes them hard to use for decision-making. Strategies to promote the use of evidence to decision makers are required, and evidence summaries have been suggested as a facilitator. Evidence summaries include policy briefs, briefing papers, briefing notes, evidence briefs, abstracts, summary of findings tables, and plain language summaries. There are many organizations developing and disseminating systematic review evidence summaries for different populations or subsets of decision makers. However, evidence on the usefulness and effectiveness of systematic review summaries is lacking. We present an overview of the available evidence on systematic review evidence summaries.

The effectiveness of evidence summaries on health policymakers and health system managers use of evidence from systematic reviews: a systematic review.

BACKGROUND: Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which make them hard to use for decision-making. There are many organizations that develop and disseminate derivative products, such as evidence summaries, from systematic reviews for different populations or subsets of decision makers. This systematic review aimed to (1) assess the effectiveness of evidence summaries on policymakers' use of the evidence and (2) identify the most effective summary components for increasing policymakers' use of the evidence. We present an overview of the available evidence on systematic review derivative products. METHODS: We included studies of policymakers at all levels as well as health system managers. We included studies examining any type of "evidence summary," "policy brief," or other products derived from systematic reviews that presented evidence in a summarized form. The primary outcomes were the (1) use of systematic review summaries in decision-making (e.g., self-reported use of the evidence in policymaking and decision-making) and (2) policymakers' understanding, knowledge, and/or beliefs (e.g., changes in knowledge scores about the topic included in the summary). We also assessed perceived relevance, credibility, usefulness, understandability, and desirability (e.g., format) of the summaries. RESULTS: Our database search combined with our gray literature search yielded 10,113 references after removal of duplicates. From these, 54 were reviewed in full text, and we included six studies (reported in seven papers) as well as protocols from two ongoing studies. Two studies assessed the use of evidence summaries in decision-making and found little to no difference in effect. There was also little to no difference in effect for knowledge, understanding or beliefs (four studies), and perceived usefulness or usability (three studies). Summary of findings tables and graded entry summaries were perceived as slightly easier to understand compared to complete systematic reviews. Two studies assessed formatting changes and found that for summary of findings tables, certain elements, such as reporting study event rates and absolute differences, were preferred as well as avoiding the use of footnotes. CONCLUSIONS: Evidence summaries are likely easier to understand than complete systematic reviews. However, their ability to increase the use of systematic review evidence in policymaking is unclear. TRIAL REGISTRATION: The protocol was published in the journal Systematic Reviews (2015;4:122).

Treatment goal setting for complex patients: protocol for a scoping review.

INTRODUCTION: An increasing number of people are living longer with multiple health and social care needs, and may rely heavily on health system resources. When dealing with multiple conditions, patients, caregivers and healthcare providers (HCPs) often experience high treatment burden due to unclear care trajectories, a myriad of treatment decisions and few guidelines on how to manage care needs. By understanding patient and caregiver priorities, and setting treatment goals, HCPs may help improve patient outcomes and experiences. This study aims to examine the extent and nature of the literature on treatment goal setting in complex patients, identify gaps in evidence and areas for further inquiry and guide a research programme to develop definitions, measures and recommendations for treatment goal setting. METHODS AND ANALYSIS: This study protocol outlines a scoping review of the peer reviewed and the grey literature, using established scoping review methodology. Literature will be identified using a multidatabase and grey literature search strategy developed by two librarians. Papers and reports on the topic of goal setting that address complexity or complex patients will be included. Results of the search will be screened independently by two reviewers and included studies will be abstracted and charted in duplicate. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review. Working with the knowledge users on the team, we will prepare educational materials and presentations to disseminate study findings to HCPs, caregivers and patients, and at relevant national and international conferences. Results will also be published in a peer-reviewed journal.

Expression of the C-C chemokine receptor 7 mediates metastasis of breast cancer to the lymph nodes in mice.

C-C chemokine receptor 7 (CCR7) controls lymphocyte migration to secondary lymphoid organs. Although CCR7 has been implicated in targeting the metastasis of cancers to lymph nodes, the role of CCR7 in the metastasis of breast cancer, along with the molecular mechanisms that are controlled by CCR7 that target breast cancer metastasis to the lymph nodes, has yet to be defined. To explore the cellular and molecular mechanisms of breast cancer cell migration to the lymph nodes, we used the mouse MMTV-PyVmT mammary tumor cells (PyVmT) transfected with CCR7 and the human CCR7-expressing MCF10A and MCF7 mammary cell lines. We found that the CCR7 ligands CCL19 and CCL21, controlled cell migration using the ß(1)-integrin heterodimeric adhesion molecules. To define a physiological significance for CCR7 regulation of migration, we used the FVB syngeneic mouse model of metastatic breast cancer. When CCR7-negative PyVmT cells transfected with control vector were orthotopically transferred to the mammary fat pad of FVB mice, tumors metastasized to the lungs (10/10 mice) but not to the lymph nodes (0/10). In contrast, CCR7-expressing PyVmT (CCR7-PyVmT) cells metastasized to the lymph nodes (6/10 mice) and had a reduced rate of metastasis to the lungs (4/10 mice). CCR7-PyVmT tumors grew significantly faster than PyVmT tumors, which mirrored the growth in vitro, of CCR7-PyVmT, MCF7, and MCF10A mammospheres. This model provides tools for studying lymph node metastasis, CCR7 regulation of tumor cell growth, and targeting of breast cancer cells to the lymph nodes.

Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study.

BACKGROUND: Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD). METHODS: The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches. RESULTS: Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention. CONCLUSION: Socio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.

Competition at the range boundary in the slimy salamander: using reciprocal transplants for studies on the role of biotic interactions in spatial distributions.

1. Determining the factors that influence the distribution of species has been a longstanding goal in the field of ecology. New techniques such as ecological niche modelling have the potential to aid in addressing many broad questions in ecology, evolutionary biology, and behavioural ecology. 2. This study combines broad-scale ecological niche models with fine-scaled studies of biotic interactions to examine how abiotic and biotic interactions affect the spatial distribution of the terrestrial salamander species Plethodon glutinosus (northern slimy salamander), in a potential contact zone shared with Plethodon mississippi (Mississippi slimy salamander). 3. The core habitat in the interior portion of the range of P. glutinosus and the contact zone are distributed in unique environmental niche space. 4. The form of competition, inter- or intraspecific, significantly affected mass loss of adult salamanders. Salamanders lost more mass when interacting with a heterospecific. 5. Abiotic conditions strongly influenced the impact of competition on salamanders. Under stressful environmental conditions at the field site located in the contact zone, salamanders lost more mass than at the field site located in the interior of the range. 6. Furthermore, adult salamanders from range-edge populations and core populations (from the interior of the range) differed in their respective abilities to compete under the abiotic conditions in the contact zone.

Arrestin 3 mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21.

Internalization of ligand bound G protein-coupled receptors, an important cellular function that mediates receptor desensitization, takes place via distinct pathways, which are often unique for each receptor. The C-C chemokine receptor (CCR7) G protein-coupled receptor is expressed on naive T cells, dendritic cells, and NK cells and has two endogenous ligands, CCL19 and CCL21. Following binding of CCL21, 21 +/- 4% of CCR7 is internalized in the HuT 78 human T cell lymphoma line, while 76 +/- 8% of CCR7 is internalized upon binding to CCL19. To determine whether arrestins mediated differential internalization of CCR7/CCL19 vs CCR7/CCL21, we used small interfering RNA (siRNA) to knock down expression of arrestin 2 or arrestin 3 in HuT 78 cells. Independent of arrestin 2 or arrestin 3 expression, CCR7/CCL21 internalized. In contrast, following depletion of arrestin 3, CCR7/CCL19 failed to internalize. To examine the consequence of complete loss of both arrestin 2 and arrestin 3 on CCL19/CCR7 internalization, we examined CCR7 internalization in arrestin 2(-/-)/arrestin 3(-/-) murine embryonic fibroblasts. Only reconstitution with arrestin 3-GFP but not arrestin 2-GFP rescued internalization of CCR7/CCL19. Loss of arrestin 2 or arrestin 3 blocked migration to CCL19 but had no effect on migration to CCL21. Using immunofluorescence microscopy, we found that arrestins do not cluster at the membrane with CCR7 following ligand binding but cap with CCR7 during receptor internalization. These are the first studies that define a role for arrestin 3 in the internalization of a chemokine receptor following binding of one but not both endogenous ligands.